title: Neuroprotective effects of the SCR1-3 functional domain of CR1 on acute cerebral ischemia and reperfusion injury in rats.
abstract: OBJECTIVE
  Complement receptor type 1 (CR1), one of the most potent inhibitors in complement activation, shows a protective effect on cerebral ischemia/reperfusion (CI/R) injury due to its ability to bind C3b and C4b and to inactivate C3/C5 convertases. So far, no study assessed the effect of the first three short consensus repeats (SCR1-3) with low molecular weight, one of the most active functional domains of CR1, binding C4b with a powerful decay-acceleration effect on classical and alternative C3/C5 convertases pathways. Therefore, we aim to assess this effect on CI/R injury in the present study.
  
  
  METHODS
  Seventy-five adult male Sprague-Dawley rats were randomly divided into three groups: sham operation group (n = 15), CI/R group (n = 30), and CI/R group treated with CR1-SCR1-3 protein (n = 30). After middle cerebral artery occlusion (MCAO) for 1 hour and reperfusion for 24 hours, neurological motor deficits, cerebral infarct size, and biochemical parameters including myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) were assessed. Meanwhile, tissues in cerebral cortex were collected and processed for western blotting, immunohistochemistry, and HE staining.
  
  
  RESULTS
  CR1-SCR1-3 could improve neurological functions in brain with a 26.8% decrease in neurological motor deficit score and could lead to a 63.8% reduction in cerebral infarct size. Besides, pretreatment using CR1-SCR1-3 could prevent neutrophil infiltration and alleviate inflammation severity and subsequent tissue damage. Decreased C4b expression and action, as well as improved morphological changes, were also observed in cerebral tissues of CI/R+CR1-SCR1-3 rats.
  
  
  CONCLUSIONS
  CR1-SCR1-3 protein could possess a neuroprotective effect on acute CI/R injury.
authors.affiliation: Third Military Medical University, Chongqing, China.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Yang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Lu
authors.forename: Zhengqing
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015935:Complement C4b / Q000378:metabolism; D016384:Consensus Sequence; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D054730:Protein Interaction Domains and Motifs; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011951:Receptors, Complement / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index
chemical_list: D018696:Neuroprotective Agents; D011951:Receptors, Complement; D015935:Complement C4b